Originator
PFD Oral Sol,Eisai,Japan,1980
Definition
ChEBI: The dipeptide obtained by condensation of N-benzoyl-L-tyrosine with 4-aminobenzoic acid. Used as a noninvasive screening test for exocrine pancreatic insufficiency and to monitor the adequacy of supplemental pancreatic t
erapy, it is given by mouth: the amount of 4-aminobenzoic acid and its metabolites excreted in the urine is taken as a measure of the chymotrypsin-secreting activity of the pancreas.
Manufacturing Process
A mixture was made of L-tyrosine (18.1 g, 0.1 mol) benzoyl chloride (7.0 g,
0.05 mol) and 200 ml anhydrous THF. After stirring at reflux for 2 hours, the
mixture was cooled to room temperature, and the precipitate of tyrosine
hydrochloride filtered off (11 g, 46 meq. Cl-). The THF was evaporated and
the residue extracted with CCl4 (3 X 100 ml at reflux, discarded) and then
dissolved in ethyl acetate (200 ml) filtering off insolubles. The ethyl acetate
solution was evaporated to yield 132 g solid product, MP 159°-162°C (93%).
The tyrosine was recovered (8 g) by neutralization with aqueous alkali, from
the hydrochloride.
A solution was made of N-benzyl-L-tyrosine (5.7 g, 20 mmols) and Nmethylmorpholine (2.04 g, 20 mmols) in 60 ml of THF, at -15°C, and to it was
added ethyl chloroformate (2.08 g, 20 mmols). After 12 minutes, paminobenzoic acid (2.74 g, 20 mmols) dissolved in 25 ml of THF and 0.38 g of
p-toluenesulfonic acid (2 mmols) were added, and the temperature allowed to
rise to 5°C. After 2 hours and forty minutes, the mixture was poured into l
liter of 0.1 N cold HCl, stirred one-half hour, filtered and dried, to give 8,7 g,
MP 192°-223°C. The product was recrystallized from 90 ml methanol and 40
ml water, to give 6 g (74%) of product, N-benzoyl-L-tyrosyl-p-aminobenzoic acid, MP 240°-242°C.
